Antibody-Dependent Cellular Phagocytosis and Cytotoxicity in Patients With LGI1 and CASPR2 Encephalitis
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND OBJECTIVES: Antibodies against LGI1 and CASPR2 (LGI1/CASPR2-IgG) associate with forms of autoimmune encephalitis (AE) that improve with immunotherapy but often show long-term residual disability. We aimed to investigate whether autoantibody effector functions contribute to pathogenic mechanisms and might act as prognostic biomarkers in patients with LGI1/CASPR2-AE. METHODS: We included patients with LGI1/CASPR2-AE, sufficient clinical information, and 1 serum sample available. We assessed the functional profile of LGI1/CASPR2-IgG using in vitro cell-based assays for complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC). Outcome was measured using the modified Rankin Scale (mRS) and the Clinical Assessment Scale in AE. RESULTS: = 0.014). DISCUSSION: ADCC and ADCP, but not CDC, are common effector functions of LGI1/CASPR2-IgG, and their presence correlates with long-term poor outcome, suggesting that they might represent a useful prognostic biomarker and suggest additional pathogenic mechanisms. We provide the proof- of principle for a framework that could be applied to other autoantibody-mediated disorders.
Authors: Pietro Businaro, Stefano Masciocchi, Silvia Scaranzin, Chiara Morandi, Federica Zuliani, Antonio Malvaso, Denise Cerne, Paolo Barone, Antonella Toriello, Carla Arbasino, Silvia Cenciarelli, Irene Volonghi, Silvia Casagrande, Stefano Nassani, Marco Currò-Dossi, Sara Micheli, Francesco Fattapposta, Alvino Bisecco, Carmela Leone, Enrico Marchioni, Diego Franciotta, Marianna Spatola, Elisabetta Zardini, Luana Benedetti, Matteo Gastaldi
Institutions: University of Pavia, Fondazione Istituto Neurologico Nazionale Casimiro Mondino, University of Salerno, AOU San Giovanni di Dio e Ruggi d'Aragona, Azienda Socio Sanitaria Territoriale di Pavia, Città di Castello Hospital, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Provincia Autonoma di Trento, Presidio Ospedaliero, Ospedale Infermi di Rimini, Ospedale di Spoleto, Sapienza University of Rome, University of Campania "Luigi Vanvitelli", Ospedale Maria Vittoria, Ospedale Santa Chiara, Fundació Clínic per a la Recerca Biomèdica, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, CaixaResearch Institute, Universitat de Barcelona
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,450
Awards: G3323308467, G8142160590
OpenAlex ID: W7129696490
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